Biomarkers of immunosuppressant organ toxicity after transplantation: status, concepts and misconceptions

Expert Opin Drug Metab Toxicol. 2011 Feb;7(2):175-200. doi: 10.1517/17425255.2011.544249.

Abstract

Introduction: A major challenge in transplantation is improving long-term organ transplant and patient survival. Immunosuppressants protect the transplant organ from alloimmune reactions, but sometimes also exhibit limiting side effects. The key to improving long-term outcome following transplantation is the selection of the correct immunosuppressive regimen for an individual patient for minimizing toxicity while maintaining immunosuppressive efficacy.

Areas covered: Proteomics and metabolomics have the potential to develop sensitive and specific diagnostic tools for monitoring early changes in cell signal transduction, regulation and biochemical pathways. Here, we review the steps required for the development of molecular markers from discovery, mechanistic and clinical qualification to regulatory approval, and present a critical discussion of the current status of molecular marker development as relevant for the management and individualization of immunosuppressive drug regimens.

Expert opinion: Although metabolomics and proteomics-based studies have yielded several candidate molecular markers, most published studies are poorly designed, statistically underpowered and/or often have not gone beyond the discovery stage. Most molecular marker candidates are still at an early stage. Due to the high complexity of and the resources required for diagnostic marker development, initiatives and consortia organized and supported by funding agencies and regulatory agencies will be critical.

Publication types

  • Research Support, N.I.H., Extramural
  • Review

MeSH terms

  • Biomarkers / analysis*
  • Biomarkers / metabolism
  • Genotype
  • Humans
  • Immunosuppressive Agents / adverse effects*
  • Immunosuppressive Agents / therapeutic use
  • Kidney Transplantation / adverse effects
  • Kidney Transplantation / immunology*
  • Metabolome
  • Phenotype
  • Proteomics
  • Signal Transduction

Substances

  • Biomarkers
  • Immunosuppressive Agents